Interleultin‐2 treatment‐associated eosinophilia is mediated by interleultin‐5 production

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Abstract
Summary During a trial using recombinant human interleukin-2 (rhIL-2) immunotherapy for acute myeloblastic leukaemia (AML) in remission, eosinophilia was observed in all patients. We used in-vitro clonogenic assays to investigate the mechanism of the eosinophilia in five patients. The mean eosinophil count increased from 0.05 ± 109/1 before rhTL-2 to 0.98 ± 109/1 within 48 h of stopping the infusion, and an exponential correlation between the pre-treatment lymphocyte CD4:CD8 ratio and the maximum eosinophil count was observed. KhIL-2 did not stimulate eosinophil colony formation by normal bone marrow. However, serum collected from patients during rhIL-2 infusion was a potent stimulator of eosinophil colony forming units (CFU-Eo), but had no significant stimulatory effect on granulocyte-macrophage colony forming units (CFU-GM). The CFU-Eo stimulation by pre-treatment serum was 2.8-fold higher than control serum. Serum collected during treatment stimulated CFIJ-Eo 12 times more than control serum (P<045). By pre-incubating patient serum, collected during rhIL-2 treatment, with monoclonal antibodies to murine IL-5. or human granulocyte-macrophage colony stimulating factor (GM-CSF). a reduction of 80% and 38% respectively in eosinophil and GM colony production was found. The CFU-Eo stimulating effect of patient serum was in the range of the CFU-Eo stimulating effect of normal serum, after the addition of 5 u/ml of recombinant murine IL-5. The results suggest that eosinophilia was caused by IL-5 and GM-CSF production by rhIL-2 stimulated CD4 positive lymphocytes. The location on chromosomes 5 of the genes for IL-5. GM-CSF and IL-3 may be associated with regulation of expression. by a common mechanism. of all the factors known to be involved in eosinophil production. This mechanism may be activated by IL-2 stimulation. The separate location on chromosome 17 of the G-CSF gene may explain the ability of IL-2 to produce a distinct stimulus to eosinophil but not neutrophil production.